Haematologica 2003 - Supplements

9.3 Treatment of bone disease.
245
THERAPY WITH BISPHOSPHONATES ENHANCES
OVERALL SURVIVAL IN PATIENTS WITH MULTIPLE
MYELOMA
Mayte Orero, Rosa Collado, Jose Hueso, Carmen Mora,
Maribel Orts, Pedro L. Perez, Francisco Ibañez, Alejandro
Pacios, Amparo Miguel-Sosa, Felix Carbonell
Hematología, Hospital General Universitario de Valencia (España)
INTRODUCTION. Bisphosphonates (BPs), wich are routinely
used in multiple myeloma (MM) patients, provide significant
protection against skeletal complications and hipercalcemia. BPs
have been shown to cause cell cycle arrest and apoptosis in MM
cells. However, most in vivo studies fail to reproduce the antitumor
effect of BPs and little is known about the efficacy of BPs
on malignant plasma cells in vivo.
OBJECTIVE. The main goal of this study was to investigate the
effect of the BPs in response to chemotherapy and survival in
patients with MM.
PATIENTS-METHODS. We have reviwed 72 patients (median
age 69 y; 35 F, 37 M; 31 Ig G, 29 Ig A, 11 Bence-Jones and 1
non secretor; 7 stage I, 15 stage II and 50 stage III disease) with
newly-diagnosed myeloma of whom 65 received chemotherapy
(melphalan and prednisone in 44, polychemotherapy in 16 and
autotransplantation in 5 patients) and 7 MM I stage were not
treated with the actual protocol. Thirty of these patients were
regularly treated with BPs (pamidronate 90 mg/monthly). We
compared two groups of patients: treated with BPs (30) and the
historical patients no treated (42) that not showed significant
differences in the following parameters: age, sex, stage, bone
lytic lesions, M-band Ig class, percentage of peripheral blood
plasma cells, hemoglobin, percentage of bone marrow plasma
cells, creatinine, calcium, LDH, beta-2-microglobulin, RCP and
proteinuria.
RESULTS. The number of patients that responsed to
chemotherapy was higher in MM patients with BPs (65,4%) than
in the other patients (44,7%), but this difference was not
significant.The overall survival was significantly better in
patients with BPs treatment (49 ± 9,9 months vs 26 ± 3,7 months,
p = 0,03).
CONCLUSION. The association of BPs to the treatment displays
an important benefit in the overall survival of MM patients. This
effect could be attributed to this potential anti-tumor activity in
vivo.
246
Bisphosphonates in Multiple Myeloma: A single
institution experience of 30 patients with Advanced
Disease
Dr. Hemant Malhotra, Dr. Dwarka P Agarwal
SMS Medical College Hospital, Jaipur, INDIA
A Leukemia Lymphoma & Myeloma Clinic was established at
the SMS Medical College Hospital, Jaipur, India in 1992. The
present work reports the use of bisphosphonates in 30 newly
diagnosed patients of advanced Multiple Myeloma (Salmon
Durie stage III) registered at this clinic. There were 26 patients
with stage IIIA and 4 patients with stage IIIB myeloma. There
were 18 males and 12 females with the mean age of 54 years
(range 38 to 72 years). Twenty two patients were given 6 cycles
of standard infusional VAD (Vincristin, Adriamycin &
Dexamethasone) Chemotherapy while 8 patients received 12
cycles of intermittant oral M+P (Melphalan + Prednisolone).
Twenty four patients were given 90 mg of Pamidronate every 4
weekly as a 3 hour intravenous infusion while 6 patients received
4 mg of Zoledronic acid as a half hour infusion. Bisphosphonates
were continued for 12 months and then stopped. Patients were
evaluated monthly. Effectively of the bisphosphonates was
assessed by tabulation of all skeletal events, incidence of
pathological fractures, incidence of radiotherapy to painful bony
disease and evaluation of analgesic use for bone pains and its
severity as assessed by a detailed questionnaire.
Overall response rate (RR) was 73% (22 out of 30) with a RR of
86% (19 out of 22) in the VAD group and 37% (3 out of 8) in the
M+P group. Four (18%) patients in the VAD group should a
complete response. All patients have been followed-up for a
median period of 17 months (range 11 to 42 months).
There were 5 (16%) skeletal events, 3 (10%) pathological
fractures and 4 (13%) patients required Radiotherapy to bony
lesions. Bony pain and analgesic use was significantly reduced
within the first two months of treatment in 14 (47%) patients and
was significantly reduced in 22 patients (73%) after six months of
treatment. Only one patient had hypercalcemia at presentation
which resolved after one cycle of chemotherapy and Zoledronic
acid. Except for allergic rash in one patient after Pamidronate,
there were no adverse events reported after bisphosphonate
treatment.
Even though this is a small study with relatively short follow-up,
we conclude that bisphosphonate treatment is well tolerated and
effective in reducing bone pains and skeletal morbidity in patients
of advanced multiple myeloma.
247
Cost of skeletal complications in patients with multiple
myeloma
Thomas Delea, James McKiernan, Martin Liss, John
Edelsberg, Jane Brandman, Jennifer Sung, Monika Raut,
Gerry Oster
Policy Analysis Inc., Brookline, MA, Novartis Pharmaceuticals
Corp., East Hanover, NJ, Columbia University, New York, NY
Background: Multiple myeloma patients often experience
skeletal-related complications including pathological fracture,
hypercalcemia, pain requiring surgery, radiotherapy, or opioid
analgesics, or spinal cord compression (collectively, skeletalrelated
events [SREs]). SREs may result in increased morbidity
and medical care costs. In the Netherlands, the estimated average
cost attributable to SREs in prostate cancer patients in 1998 was
6,973 Euros (7,300 $US 2002).1 The cost of SREs in multiple
myeloma patients is unknown. Methods: The objective of this
study was to estimate the costs of SREs in US multiple myeloma
patients. We used data from large health-insurance claims
database spanning 7/94-6/02 and linked mortality data from the
US Social Security Administration. Study subjects included all
persons with (1) >2 encounters with a diagnosis of multiple
myeloma; and (2) presence of >1 SRE. SREs were identified
based on the occurrence, on or after the date of first diagnosis of
multiple myeloma, of (1) >1 encounter with a diagnosis of
pathological fracture, spinal cord compression, or hypercalcemia,
or (2) >1 bone surgery or radiotherapy procedure, or (3) initiation
of opioid analgesic therapy. The primary measure of interest was
the expected lifetime cost of SRE-related care, which was
estimated using Kaplan-Meier methods. Results: We identified
835 multiple myeloma patients, of whom 352 (42%) experienced
>1 SRE. Mean age of patients with SREs was 66 years. Median
survival from date of first SRE was 28 months. Expected lifetime
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